Dietary phytochemicals in cancer prevention and therapy: a complementary approach with promising perspectives
TL;DR: The aim of the present literature review is to summarize current knowledge of the dietary phytochemicals with proven antitumor activity, with a special emphasis placed on their molecular targets.
Abstract: The population is aging. Over the coming years, the incidence of age-related chronic diseases such as cancer is expected to continue to increase. Phytochemicals, which are non-nutritive chemicals found in plants and food, have emerged as modulators of key cellular signaling pathways exerting proven anticancer effects. The challenge now is to develop personalized supplements comprised of specific phytochemicals for each clinical situation. This will be possible once a better understanding is gained of the molecular basis explaining the impact of phytochemicals on human health. The aim of the present literature review is to summarize current knowledge of the dietary phytochemicals with proven antitumor activity, with a special emphasis placed on their molecular targets. Also discussed are the limits of existing research strategies and the future directions of this field.
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TL;DR: One of the promising solutions lies in nanoformulation of polyphenols that prevents their degradation and thus enables significantly higher concentrations to reach the target cells, resulting in lowering of the required therapeutic dose and in multitargeted action.
Abstract: Being secondary plant metabolites, polyphenols represent a large and diverse group of substances abundantly present in a majority of fruits, herbs and vegetables. The current contribution is focused on their bioavailability, antioxidative and anticarcinogenic properties. An overview of extraction methods is also given, with supercritical fluid extraction highlighted as a promising eco-friendly alternative providing exceptional separation and protection from degradation of unstable polyphenols. The protective role of polyphenols against reactive oxygen and nitrogen species, UV light, plant pathogens, parasites and predators results in several beneficial biological activities giving rise to prophylaxis or possibly even to a cure for several prevailing human diseases, especially various cancer types. Omnipresence, specificity of the response and the absence of or low toxicity are crucial advantages of polyphenols as anticancer agents. The main problem represents their low bioavailability and rapid metabolism. One of the promising solutions lies in nanoformulation of polyphenols that prevents their degradation and thus enables significantly higher concentrations to reach the target cells. Another, more practiced, solution is the use of mixtures of various polyphenols that bring synergistic effects, resulting in lowering of the required therapeutic dose and in multitargeted action. The combination of polyphenols with existing drugs and therapies also shows promising results and significantly reduces their toxicity.
638 citations
Cites background from "Dietary phytochemicals in cancer pr..."
...Flavonoids represent the largest part of dietary polyphenols (up to 60%) [5]....
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...Anti-angiogenic action of apigenin is similar to that of EGCG, as well as inhibition of tumor growth, suppression of progression and invasion of tumor and prevention of metastasis through altering Bcl-2 associated X protein (Bax)/Bcl-2 ratio, MAPK and PI3/Akt signaling and through modulation of insulin-like growth factor (IGF), VEGF, MMP’s and transforming growth factor TGF-β1 [13,93]....
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...Similarly to EGCG, quercetin blocks proliferation, invasion, migration, metastasis and angiogenesis mainly through inhibition of several MMPs [5,81,82]....
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...It has been experimentally confirmed that polyphenols not only prevent various diseases but also impact on the disease propagation, suppress progression and even contribute to the healing process [5,12]....
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...The polyphenols represent a large group of at least 10,000 different compounds that contain one or more aromatic rings with one or more hydroxyl groups attached to them [4,5]....
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TL;DR: In this review, an in-depth analysis of the most innovative advances in basic and applied cancer research is provided.
Abstract: Every year, cancer is responsible for millions of deaths worldwide and, even though much progress has been achieved in medicine, there are still many issues that must be addressed in order to improve cancer therapy. For this reason, oncological research is putting a lot of effort towards finding new and efficient therapies which can alleviate critical side effects caused by conventional treatments. Different technologies are currently under evaluation in clinical trials or have been already introduced into clinical practice. While nanomedicine is contributing to the development of biocompatible materials both for diagnostic and therapeutic purposes, bioengineering of extracellular vesicles and cells derived from patients has allowed designing ad hoc systems and univocal targeting strategies. In this review, we will provide an in-depth analysis of the most innovative advances in basic and applied cancer research.
372 citations
Cites background from "Dietary phytochemicals in cancer pr..."
...proliferative and pro-apoptotic properties, and have been introduced as complementary therapies for cancer [4, 5, 103]....
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TL;DR: Evidence suggests that F&V have the strongest effects in relation to prevention of CVDs, noting a nonlinear threshold effect of 800 g per day (i.e., about 5 servings a day).
Abstract: Fruit and vegetables (FV the 2015–2020 U.S. Dietary Guidelines for Americans recommend that F&V constitute one-half of the plate at eac...
252 citations
Cites background from "Dietary phytochemicals in cancer pr..."
...Polyphenols have been shown the capacity to block or attenuate initiation or to suppress the stages of promotion and progression of carcinogenesis by controlling proliferation, apoptosis, cell cycle progression, inflammation, angiogenesis, invasion and metastasis (Gonzalez-Vallinas et al. 2013)....
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TL;DR: Focus will be on some promising polyphenolics such as resveratrol, curcumin, and genistein; alkaloids namely berberine, noscapine, and colchicine; terpenoids; and the organosulfur compound sulforaphane.
Abstract: Despite remarkable progress in the discovery and development of novel cancer therapeutics, cancer remains the second leading cause of death in the world. For many years, compounds derived from plants have been at the forefront as an important source of anticancer therapies and have played a vital role in the prevention and treatment of cancer because of their availability, and relatively low toxicity when compared with chemotherapy. More than 3000 plant species have been reported to treat cancer and about thirty plant-derived compounds have been isolated so far and have been tested in cancer clinical trials. The mechanisms of action of plant-derived anticancer drugs are numerous and most of them induce apoptotic cell death that may be intrinsic or extrinsic, and caspase and/or p53-dependent or independent mechanisms. Alternative modes of cell death by plant-derived anticancer drugs are emerging and include mainly autophagy, necrosis-like programmed cell death, mitotic catastrophe, and senescence leading to cell death. Considering that the non-apoptotic cell death mechanisms of plant-derived anticancer drugs are less reviewed than the apoptotic ones, this paper attempts to focus on such alternative cell death pathways for some representative anticancer plant natural compounds in clinical development. In particular, emphasis will be on some promising polyphenolics such as resveratrol, curcumin, and genistein; alkaloids namely berberine, noscapine, and colchicine; terpenoids such as parthenolide, triptolide, and betulinic acid; and the organosulfur compound sulforaphane. The understanding of non-apoptotic cell death mechanisms induced by these drugs would provide insights into the possibility of exploiting novel molecular pathways and targets of plant-derived compounds for future cancer therapeutics.
220 citations
Cites background from "Dietary phytochemicals in cancer pr..."
...Plant polyphenols are rich in the human diet and are known to possess anticancer properties by interfering with the different stages of cancer development [18]....
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TL;DR: In this article, the authors focus on the effects of ultrasound assisted extraction on the yield and composition of polyphenol extracts and the antioxidant, anticancer, and antimicrobial properties of phenolic extracts.
Abstract: Ultrasound assisted extraction (UAE) is widely used in recent times for its benefits, but it is difficult to find literature that comprehensively addresses the effect of UAE-specific parameters such as temperature, frequency, power, solvent type, and solvent to material ratio on extracted compounds and their functionality. There is no review done so far on the effects of all UAE parameters on polyphenol extracts to guide the design of extraction protocols. This review therefore focuses on the effects of UAE parameters on the yield and composition, as well as the effects of the UAE on the antioxidant, anticancer, and antimicrobial properties of phenolic extracts. Higher extraction temperatures above 50 °C are degradative to polyphenols in extracts; lower frequencies within the power ultrasound range below 40 kHz are most effective; polyphenol yield generally increases with increasing power, but with a threshold, beyond which no significant increase is observed; and higher ultrasound power produces free hydroxyl radicals which degrade polyphenols, especially in the presence of high water content. A comparative assessment of literature showed that, UAE does not only contribute to increased extraction yield of polyphenols, but also better preserves and increases the biological activity of polyphenol extracts compared to traditional maceration and Soxhlet extraction. A full picture of UAE is given to serve as a reference material on the control of UAE parameters for desired results and efficiency.
212 citations
References
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TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.
51,099 citations
7,570 citations
Book•
01 Jan 1996
TL;DR: This is the first in a planned series of 10 volumes that will attempt to "summarize epidemiological knowledge about all major conditions and most risk factors" and use historical trends in main determinants to project mortality and disease burden forward to 2020.
Abstract: This is the first in a planned series of 10 volumes that will attempt to "summarize epidemiological knowledge about all major conditions and most risk factors;...generate assessments of numbers of deaths by cause that are consistent with the total numbers of deaths by age sex and region provided by demographers;...provide methodologies for and assessments of aggregate disease burden that combine--into the Disability-Adjusted Life Year or DALY measure--burden from premature mortality with that from living with disability; and...use historical trends in main determinants to project mortality and disease burden forward to 2020." This first volume includes chapters summarizing results from the project as a whole. (EXCERPT)
7,154 citations
TL;DR: No reduction in the incidence of lung cancer among male smokers is found after five to eight years of dietary supplementation with alpha-tocopherol or beta carotene, and this trial raises the possibility that these supplements may actually have harmful as well as beneficial effects.
Abstract: Background. Epidemiologic evidence indicates that diets high in carotenoid-rich fruits and vegetables, as well as high serum levels of vitamin E (alpha-tocopherol) and beta carotene, are associated with a reduced risk of lung cancer. Methods. We performed a randomized, double-blind, placebo-controlled primary-prevention trial to determine whether daily supplementation with alpha-tocopherol, beta carotene, or both would reduce the incidence of lung cancer and other cancers. A total of 29,133 male smokers 50 to 69 years of age from southwestern Finland were randomly assigned to one of four regimens: alpha-tocopherol (50 mg per day) alone, beta carotene (20 mg per day) alone, both alpha-tocopherol and beta carotene, or placebo. Follow-up continued for five to eight years. Results. Among the 876 new cases of lung cancer diagnosed during the trial, no reduction in incidence was observed among the men who received alpha-tocopherol (change in incidence as compared with those who did not, -2 percent; 95 percent confidence interval, -14 to 12 percent). Unexpectedly, we observed a higher incidence of lung cancer among the men who received beta carotene than among those who did not (change in incidence, 18 percent; 95 percent confidence interval, 3 to 36 percent). We found no evidence of an interaction between alpha-tocopherol and beta carotene with respect to the incidence of lung cancer. Fewer cases of prostate cancer were diagnosed among those who received alpha-tocopherol than among those who did not. Beta carotene had little or no effect on the incidence of cancer other than lung cancer. Alpha-tocopherol had no apparent effect on total mortality, although more deaths from hemorrhagic stroke were observed among the men who received this supplement than among those who did not. Total mortality was 8 percent higher (95 percent confidence interval, 1 to 16 percent) among the participants who received beta carotene than among those who did not
4,357 citations